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Review
. 2021 Apr 1;22(7):3658.
doi: 10.3390/ijms22073658.

Mammalian Neuropeptides as Modulators of Microbial Infections: Their Dual Role in Defense versus Virulence and Pathogenesis

Daria Augustyniak  1 , Eliza Kramarska  1   2 , Paweł Mackiewicz  3 , Magdalena Orczyk-Pawiłowicz  4 , Fionnuala T Lundy  5
Affiliations
Review

Mammalian Neuropeptides as Modulators of Microbial Infections: Their Dual Role in Defense versus Virulence and Pathogenesis

Daria Augustyniak et al. Int J Mol Sci. .

Abstract

The regulation of infection and inflammation by a variety of host peptides may represent an evolutionary failsafe in terms of functional degeneracy and it emphasizes the significance of host defense in survival. Neuropeptides have been demonstrated to have similar antimicrobial activities to conventional antimicrobial peptides with broad-spectrum action against a variety of microorganisms. Neuropeptides display indirect anti-infective capacity via enhancement of the host's innate and adaptive immune defense mechanisms. However, more recently concerns have been raised that some neuropeptides may have the potential to augment microbial virulence. In this review we discuss the dual role of neuropeptides, perceived as a double-edged sword, with antimicrobial activity against bacteria, fungi, and protozoa but also capable of enhancing virulence and pathogenicity. We review the different ways by which neuropeptides modulate crucial stages of microbial pathogenesis such as adhesion, biofilm formation, invasion, intracellular lifestyle, dissemination, etc., including their anti-infective properties but also detrimental effects. Finally, we provide an overview of the efficacy and therapeutic potential of neuropeptides in murine models of infectious diseases and outline the intrinsic host factors as well as factors related to pathogen adaptation that may influence efficacy.

Keywords: adhesion; antimicrobial activity; bacterial infections; defense; fungal infections; invasion; neuropeptides; pathogenesis; protozoan infections; virulence.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Overview of mechanisms of pathogenesis and virulence traits modulated by neuropeptides. The question mark indicates that the given mechanism is putative.
Figure 2
Figure 2
Potential cleavage sites in neuropeptide sequences subjected to selected bacterial proteases. The sites were identified using PROSITE scanning program and cleavage patterns created based on data available in MEROPS database for the individual peptidases. In the pattern, we considered three positions before and after the cleavage site, i.e., P3 P2 P1 P1’ P2’ P3’. Antimicrobial peptide LL-37 was shown for comparison.
See this image and copyright information in PMC

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